Methods and systems for detecting biomolecular binding using terahertz radiation

Abstract

Provided herein are methods and systems for detecting biomolecular binding events using gigahertz or terahertz radiation. The methods and systems use low-energy spectroscopy to detect biomolecular binding events between molecules in an aqueous solution. The detected biomolecular binding events include, for example, nucleic acid hybridizations, antibody/antigen binding, and receptor/ligand binding.

1 . A method to detect an analyte in a biological sample, comprising: 
 a) contacting the biological sample with a first molecule immobilized on a substrate, wherein the first molecule is suspected of binding the analyte;    b) impinging the first molecule with a gigahertz or terahertz input radiation; and    c) detecting a vibrational spectrum of the first molecule, wherein a shift in the vibrational spectrum, or decrease in an intensity level of the vibrational spectrum, compared to a vibrational spectrum of a first molecule not associated with the analyte, is indicative of the presence of the analyte in the sample.    
     
     
         2 . The method of  claim 1 , wherein the biological sample is from blood, urine, saliva, tissue, ejaculate, serum, cerebrospinal fluid, pleural fluid, ascites fluid, sputum, stool, or a biopsy sample.  
     
     
         3 . A method to identify an agent that affects a biomolecular binding, comprising: 
 a) contacting a first molecule, a second molecule, and the agent, wherein the first molecule binds to the second molecule;    b) impinging the first molecule with a gigahertz or terahertz light source; and    c) detecting a vibrational spectrum of the first molecule, wherein a shift in the vibrational spectrum or a change in intensity level of the vibrational spectrum, compared to a vibrational spectrum of a first molecule bound to the second molecule in the absence of the agent, identifies the agent that affects the molecule binding.    
     
     
         4 . The method of  claim 3 , wherein the first molecule is a nucleic acid molecule.  
     
     
         5 . The method of  claim 3 , wherein the first molecule is a protein.  
     
     
         6 . The method of  claim 5 , wherein the protein is an antibody.  
     
     
         7 . A method of detecting a biomolecular binding event, the method comprising: 
 a) preparing a sample comprising a first molecule and a second molecule;    b) directing an input radiation at the sample, whereby the input radiation excites the sample without causing fluorescence; and    c) detecting an exit radiation traveling from the sample, wherein a shift in vibrational frequency or a change in intensity level of the exit radiation compared to the exit radiation detected for a first molecule not bound to the second molecule, is indicative of a biomolecular interaction.